Gluconeogenesis
GLUCONEOGENESIS
- Synthesis of glucose from non-carbohydrate precursors
- Occurs mostly in the liver and minor process in kidney
- Kidney produces 10% total glucose during overnight fast
- Produced by exercising muscle and red blood cells
- Reconverted to pyruvate in liver
- TAG hydrolyzes to glycerol in adipose tissue
- Liver converts glycerol to DHAP in 2 step reaction
- Major source of glucose during extended fast
- Muscle tissue hydrolysis releases glucogenic AA during fast
- AA produce alpha-ketoacids in the liver: enter CAC or gluconeogenesis
- Clears blood lactate from red blood cells and exercising muscle
- Maintains blood glucose during high fat diet or fast
1. Pyruvate carboxylase (mitochondrial matrix)
- converts pyruvate to oxaloacetate
- Requires 1 ATP, biotin and 1 CO2
2. Phosphoenol carboxykinase (cytosol)
- Preceded by malate shuttle (1 NADH consumed and 1 NADH produced)
- Converts oxaloacetate to phosphoenolpyruvate (PEP)
- Consumes 1 GTP and releases 1 CO2
PEP converted to glyceraldehyde 3-phosphate in 4 reversible reactions: 1 ATP and 1 NADH consumed (double energy inputs, substrates and products)
Glyceraldehyde 3-phosphate reversibly combines w/ DHAP to form fructose 1,6-bisphosphate
3. Fructose 1,6-bisphosphatase (cytosol)
- Produces fructose 6-phosphate
- Consumes 1 H20 and releases 1 Pi
Fructose 6-phosphate reversibly converts to glucose 6-phosphate
4. Glucose 6-phosphatase (ER membrane-bound)
- Translocates glucose 6-phosphate to the ER lumen and removes Pi
- Consumes 1 H2O